title: Dexamethasone differentially regulates renal and duodenal calcium-processing genes in calbindin-D9k and -D28k knockout mice.
abstract: Glucocorticoids (GCs) appear to downregulate active calcium-transporting genes in the duodenum, resulting in GC-induced calcium-absorbing disorder. In this study, we examined the effects of GCs on calcium-processing genes in the duodenum and kidney and the compensatory mechanism in calbindin-D9k (CaBP-9k) and calbindin-D28k (CaBP-28k) knockout (KO) mice. In the duodenum, we observed compensatory increases in transient receptor potential vanilloid 6 (TRPV6) mRNAs in both calbindin KO mice and CaBP-9k transcripts in CaBP-28k KO mice, and their expressions were decreased by addition of a synthetic GC, dexamethasone (Dex, 10 mg kg(-1)). In addition, the expression of plasma membrane calcium ATPase 1b (PMCA1b) underwent a compensatory increase in CaBP-9k KO mice, and was blocked by Dex, while the mRNA level of duodenal sodium-calcium exchanger 1 was not altered by KO status or Dex. The renal transcriptional levels of TRPV5 in CaBP-9k KO and CaBP-9k in CaBP-28k KO mice were upregulated in a compensatory manner, while the TRPV6 gene was downregulated following treatment with Dex in the kidney of CaBP-28k KO mice. The immunological location of these duodenal proteins as a primary target of Dex-involved regulation was not altered by Dex or KO status. To elucidate potential mechanism(s) of Dex-induced compensatory gene expression, the levels of GC receptor (GR), vitamin D receptor (VDR) and parathyroid hormone receptor (PTHR) mRNA was also measured in these tissues. Duodenal VDR transcripts were induced in a compensatory manner in both types of KO mice, and were decreased by Dex. In addition, serum corticosterone levels in both KO mice were lower than in wild-type mice. In conclusion, these results suggest that duodenal TRPV6 and CaBP-9k genes appear to be a primary target for GC-induced calcium-absorbing disorder, through direct regulation of duodenal VDR transcription.
authors.affiliation: Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Man-Hee
authors.initials: MH
authors.lastname: Kim
authors.forename: Geun-Shik
authors.initials: GS
authors.lastname: Lee
authors.forename: Eui-Man
authors.initials: EM
authors.lastname: Jung
authors.forename: Kyung-Chul
authors.initials: KC
authors.lastname: Choi
authors.forename: Goo-Taeg
authors.initials: GT
authors.lastname: Oh
authors.forename: Eui-Bae
authors.initials: EB
authors.lastname: Jeung
mesh_terms: D000042:Absorption; D000818:Animals; D064092:Calbindin 1; D064026:Calbindins; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D004386:Duodenum / Q000378:metabolism*; D005938:Glucocorticoids / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000235:genetics / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism
chemical_list: C576499:Calb1 protein, mouse; D064092:Calbindin 1; D064026:Calbindins; D015220:Calcium Channels; D005938:Glucocorticoids; D012333:RNA, Messenger; D044168:Receptor, Parathyroid Hormone, Type 1; D018167:Receptors, Calcitriol; D011965:Receptors, Glucocorticoid; D064030:S100 Calcium Binding Protein G; C576507:S100g protein, mouse; D019831:Sodium-Calcium Exchanger; D050916:TRPV Cation Channels; C492240:Trpv5 protein, mouse; C446923:Trpv6 protein, mouse; D003907:Dexamethasone; D053499:Plasma Membrane Calcium-Transporting ATPases; C506954:Atp2b1 protein, mouse; D002118:Calcium